Ch.18: Ethers and Epoxides; Thiols and Sulfides

1. Ch.18: Ethers and Epoxides; Thiols and Sulfides Dr. Sivappa Rasapalli Chemistry and Biochemistry University of Massachusetts Dartmouth

2. Coverage and Objectives Coverage: • The nomenclature of alcohols • Synthesis and Nucleophilic substitution reactions of ethers • Nucleophilic Opening reactions of epoxides • Chemistry of sulfur compounds Learning objectives: • Provide both IUPAC and common names for ethers, sulfides. • Recognize the physical properties of ethers, epoxides and sulfides • Know the synthesis and chemistry of the functional groups • Write the reaction and electron-pushing (arrow-pushing) mechanism for the synthesis and reactions of the functional groups • Write the acid-catalyzed ring-opening of epoxides, and explain the observed stereochemistry of the products.

3. Nomenclature of Ethers, Epoxides, and Sulfides 18.1 Names and Properties of Ethers

4. Ethers, Epoxides, Thiols and sulfides •Ethers (ROR) can be regarded as derivatives of alcohols (ROH). •Sulfides (RSR) can be regarded as derivatives of Thols (RSH).

5. Nomenclature: Functional Class • simple ethers are named: “alkyl alkyl ether” • name the groups attached to oxygen in alphabetical order as separate words; "ether" is last word; • “dialkyl ether” if symmetric

6. name as alkoxy derivatives of alkanes Nomenclature: Substituent CH3OCH2 CH3 CH3CH2OCH2CH2CH2Cl methoxyethane 1-chloro-3-ethoxypropane CH3CH2OCH2 CH3 ethoxyethane

7. Nomenclature: Functional Class SCH3 • analogous to ethers, but replace “ether” as lastword in the name by “sulfide.” CH3SCH2 CH3 ethyl methyl sulfide cyclopentyl methyl sulfide CH3CH2SCH2 CH3 diethyl sulfide

8. Nomenclature: Substituent SCH3 • name as alkylthio derivatives of alkanes CH3SCH2 CH3 methylthioethane (methylthio)cyclopentane CH3CH2SCH2 CH3 ethylthioethane

9. Names of Cyclic Ethers Oxirane(Ethylene oxide) Oxolane(tetrahydrofuran) Oxetane 1,4-Dioxane Oxane(tetrahydropyran) O O O O O O

10. Names of Cyclic Sulfides Thiirane Thiolane Thietane Thiane S S S S

11. Examples of Nomenclature

13. Structure and BondinginEthers and Epoxides

14. Bond angles at oxygen are sensitiveto steric effects 108.5° 105° O C(CH3)3 (CH3)3C 112° 132° O O H H CH3 H O CH3 CH3

15. An oxygen atom affects geometry in much thesame way as a CH2 group most stable conformation of diethyl etherresembles pentane

16. An oxygen atom affects geometry in much thesame way as a CH2 group most stable conformation of tetrahydropyranresembles cyclohexane

17. Physical Properties of Ethers

18. • Boiling points (and melting points) of ethers are lower than corresponding alcohol – E.g. CH3CH2OH (bp 78°C) vs. CH3-O-CH3 (bp -25°C) • Why? No Hydrogen-bonding for ethers

19. Intermolecular hydrogenbonding possible in alcohols; not possible in alkanes or ethers. Ethers resemble alkanes more than alcoholswith respect to boiling point boiling point 36°C 35°C O 117°C OH

20. Hydrogen bonding towater possible for ethersand alcohols; not possible for alkanes. Ethers resemble alcohols more than alkaneswith respect to solubility in water solubility in water (g/100 mL) very small 7.5 O 9 OH • Solubility of acyclic ethers in water is less than that of corresponding alcohols of equal MW. – Ethers can accept H-bonds, but not donate them

21. Physical Properties-Uses Ethers are less dense than water and form the top layer when mixed with water. • Note: Diethyl ether (“ether”) is a good general purpose solvent for extracting non-polar and polar organic compounds from H2O. • Its low boiling pt (35 oC) is ideal for recovering organic solute by evaporation of ether. Solubility of cyclic ethers in water is greater than that of acyclic ethers of equal MW. • Compact shape more easily accommodated by H-bonding network of water ; Ex: Tetrahydrofuran 1,4-Dioxane completely miscible with water; important cosolvents

23. Solvation

24. Crown Ethers O O O O O O • structure cyclic polyethers derived from repeating —OCH2CH2— units • properties form stable complexes with metal ions • applications synthetic reactions involving anions 18-Crown-6

25. forms stable Lewis acid/Lewis base complex with K+ 18-Crown-6 O O O O O O K+

26. Ion-Complexing and Solubility O O O O O O O O O O O O + F– K+ benzene 18-crown-6 complex of K+ dissolves in benzene F– carried into benzene to preserve electroneutrality

27. Complexation of K+ by 18-crown-6 "solubilizes" potassium salts in benzene Anion of salt is in a relatively unsolvated state in benzene (sometimes referred to as a "naked anion") Unsolvated anion is very reactive Only catalytic quantities of 18-crown-6 are needed Application to organic synthesis KF CH3(CH2)6CH2Br CH3(CH2)6CH2F 18-crown-6 (92%) benzene

28. 18. 2 Synthesis of Ethers

29. Acid–catalyzed dehydration of Alcohols Diethyl ether prepared industrially by sulfuric acid–catalyzed dehydration of ethanol – also with other primary alcohols

30. The Williamson Ether Synthesis Reaction of metal alkoxides and primary alkyl halides and tosylates Best method for the preparation of ethers Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH

31. Example • RO-, an alkoxide ion, is both a strong nucleophile (unless bulky and hindered) and a strong base. Both SN2 (desired) and E2 (undesired side product) can occur. • Choose nucleophile and electrophile carefully. Maximize SN2 and minimize E2 reaction by choosing the R’X to have least substituted carbon undergoing substitution (electrophile). Methyl best, then primary, secondary marginal, tertiary never (get E2 instead). • Stereochemistry: the reacting carbon in R’, the electrophile which undergoes substitution, experiences inversion. The alkoxide undergoes no change of configuration.

32. Williamson’s Ether Synthesis has Limitations 1. Alkyl halide must be primary (RCH2X) 2. Alkoxides need be derived from primary, secondary or tertiary alcohols

33. Origin of Reactants

34. What happens if the alkyl halide is not primary?

35. Silver Oxide-Catalyzed Ether Formation Reaction of alcohols with Ag2O directly with alkyl halide forms ether in one step Glucose reacts with excess iodomethane in the presence of Ag2O to generate a pentaether in 85% yield

36. Addition of Alcohols to Alkenes H+ (CH3)2C=CH2 + CH3OH (CH3)3COCH3 tert-Butyl methyl ether tert-Butyl methyl ether (MTBE) was produced on a scale exceeding 15 billion pounds per year in the U.S. during the 1990s. It is an effective octane booster in gasoline, but contaminates ground water if allowed to leak from storage tanks. Further use of MTBE is unlikely.

37. Alkoxymercuration

38. Mechanism of Oxymercuration

39. Reactions of Ethers:

40. No reactions of ethers encountered to this point. Ethers are relatively unreactive. Their low level of reactivity is one reason why ethers are often used as solvents in chemical reactions, and as protecting groups for reactive –OH group. Ethers oxidize in air to form explosive hydroperoxides and peroxides. Summary of reactions of ethers

41. Acid-Catalyzed Cleavage of Ethers Ethers are generally unreactive Strong acid will cleave an ether at elevated temperature HI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)

42. Example HBr CH3CHCH2CH3 CH3CHCH2CH3 + CH3Br heat OCH3 Br (81%)

43. Mechanism CH3CHCH2CH3 CH3CHCH2CH3 O Br •• •• CH3 •• HBr Br H •• •• CH3CHCH2CH3 CH3CHCH2CH3 O •• + •• H – O •• •• CH3 •• H Br •• •• Br CH3 •• •• ••

44. Cleavage of Cyclic Ethers O HI ICH2CH2CH2CH2I 150°C (65%)

45. Mechanism ICH2CH2CH2CH2I O HI HI – •• •• I •• •• •• •• •• I •• + O •• O •• H H •• ••

46. Specific to allyl aryl ethers, ArOCH2CH=CH2 Heating to 200–250°C leads to an o-allylphenol Result is alkylation of the phenol in an ortho position Claisen Rearrangement

47. Epoxides (Oxiranes) • Three membered ring ether is called an oxirane (root “ir” from “tri” for 3-membered; prefix “ox” for oxygen; “ane” for saturated) • Also called epoxides • Ethylene oxide (oxirane; 1,2-epoxyethane) is industrially important as an intermediate • Prepared by reaction of ethylene with oxygen at 300 °C and silver oxide catalyst

48. Epoxides are Extremely Reactive

49. Preparation of Epoxides Using a Peroxyacid • Treat an alkene with a peroxyacid

50. Epoxide Ring Opening reactions: 1. Epoxide Ring Opening in Acid In acid:protonate the oxygen, establishing the very good leaving group. More substituted carbon (more positive charge although more sterically hindered) is attacked by a weak nucleophile. Very similar to opening of cyclic bromonium ion. Review that subject. Due to resonance, some positive charge is located on this carbon. Inversion occurs at this carbon. Do you see it? Classify the carbons. S becomes R.